The reader must be aware that the following information about treatment options is intended only as a compendium of treatment approaches available for people with OCD. The goal is to provide an overall understanding of these therapies sufficient to enable more informed interactions with physicians and therapists. The numerous OCD treatment options currently available, and the variability of specific OCD characteristics, are taken into account by physicians and therapists when making treatment recommendations. Better insights into these factors will, hopefully, allow patients and families to be more active participants in discussions and treatment decision-making with their OCD specialists.
The two principal types of OCD treatment are cognitive and behavioural therapy (CBT) and drugs. Evidence of clinical effectiveness has been amply demonstrated for both (18) and each has a role in OCD symptom control. Whether to begin treatment with CBT, drug treatment, or both, depends on the assessment of the type and severity of the OCD, practitioner experience and preference, and patient health and coexisting medical problems. (19). The latter must be considered carefully in order to minimize the risk of treatment noncompliance.
First line treatment with cognitive and behavioural therapy
Cognitive therapy and behavioural therapy are separate but complementary treatment methods (18, 20). At the risk of oversimplifying these specialised types of treatment, cognitive therapy focuses on the thoughts driving anxiety and distress, and uses techniques to teach patients how to cope with or avoid the triggers for obsessions. Behavioural therapy addresses the actions or other responses resulting from the disturbing thoughts.
Cognitive therapies help patients to understand their dysfunctional thoughts or beliefs. These insights help to develop greater familiarity and objectivity about the nature of their obsessions, and to develop greater awareness of circumstances that trigger these obsessive thoughts (21, 22). The treatment goals may also include the development of good coping skills, learning relaxation techniques, and skills to quickly intervene at the onset of a disturbing thought by substituting more pleasant thoughts that do not cause tension or anxiety.
The behavioral therapy most often used for those with OCD is referred to as Exposure and Response Prevention (ERP). ERP is based on the observation that when patients can resist or delay a particular compulsion, even for a short time, the magnitude of their obsessive thoughts may decrease or disappear (habituation) (23). The typical ERP procedure involves deliberate and incremental exposure to those situations or thoughts that are fearful and cause anxiety and requires patients to resist performing any compulsive actions. Of course, conducting ERP therapy can be an extremely stressful exercise, and some whose obsessions are embarrassing and humiliating are unwilling to undergo treatment. When patients complete their ERP treatment course, it has been unequivocally proven to be an effective and often sustainable first line therapy (20, 24), with as many as 50% to 60% having an initial response (18, 21, 23).
It is not yet completely clear whether CBT or SSRI drug treatment is the first line treatment of choice. The majority of studies show comparable effects between them. When outcome differences are found, they generally favour CBT over drug treatment. One study illustrates how the methods of analysis can also change conclusions (24). This investigation reported superior long-term effectiveness of ERP compared to selective serotonin reuptake inhibitors (SSRIs) (24). However, after excluding results in those patients who had prematurely discontinued their medication, the analysis showed equivalent outcomes for SSRI and ERP. Clearly, drug treatment is usually ineffective if the drug is not taken.
An analysis of a group of studies supported the relative equivalence of ERP and SSRI, but also observed that the combination of the two was superior to either used alone (25). In this report, the investigators found that the combination of CBT and drug therapy was better than each, alone. However, they also observed that this was true only with the use of selective serotonin reuptake inhibitors; non-selective drugs, such as clomipramine, showed no significant effect.
In general, although both CBT/ERP treatment and first line drug therapy have been effective in OCD, it appears that the reported levels of improvement from ERP are more consistent than drug treatment. For patients eligible for either approach, ERP may be more attractive for the reasons stated above, and also will avoid undesirable drug side effects.
Neurotransmitters (NT) as targets for drug therapy
Imbalances of certain neurotransmitters are thought to play important roles in OCD. Most current and emerging drug treatments for OCD, in different ways, are intended to mitigate the abnormal balance. A basic, but very brief, explanation of the likely roles of altered NT functions in OCD can provide more insight into drug treatment strategies for this disorder.
Numerous types of NT have functional roles in the brain that are critically essential to all aspects of brain function. NTs function by facilitating, inhibiting, or otherwise altering the nerve-signaling pathways for any or all brain functions. Many NTs are stored, released when signaled to do so, and act by then attaching to very specific sites (receptors) on the adjacent nerve. The particular NT, and the nature of its receptor, determine whether or not a nerve signal is transmitted and, if so, the strength of the signal. Thus, their actions on nerves depend upon a sequence of several steps. Abnormalities of neurotransmitter function appear to have central roles in OCD (27).
Genetic, functional brain imaging, and clinical analyses of OCD patients point to several NTs as likely contributors to the development of the disorder. These are glutamate, gamma-aminobutyric acid (GABA), serotonin (5-HT), and dopamine.
Glutamate, the most abundant NT, acts to increase the excitability of nerves. Excessive brain nerve excitability from elevated levels of glutamate and dopamine is thought to be central to OCD behaviors (9). In fact, when otherwise normal laboratory animals have glutamate levels artificially increased, they exhibit OCD-like behavior.
There also are findings to support an important role for dopamine in OCD (28). Among its NT functions, dopamine mediates compulsions, and the sense of satisfaction and pleasure from a particular experience. In a sense, compulsions can be thought of as attempts to relieve the extreme anxiety that results from obsessive thoughts. One hypothesis is that excess dopamine reinforces the sense of relief (the “pleasurable” experience) when a compulsion offsets the distress of a particular obsession.
GABA is the second most abundant NT, and has a role opposite to glutamate, acting to reduce nerve excitability throughout the nervous system including the brain. The levels of GABA in OCD patients tend to be low and insufficient to offset neurostimulation. In addition, low brain serotonin levels are regularly seen. Serotonin and several other NTs play important roles in response inhibition (29), which is particularly poor in OCD. When serotonin availability is increased with drug therapy, glutamate levels decrease and GABA levels rise, with a net effect of diminished neurostimulation (30). Thus, serotonin appears to be a modulator of excitatory nerve transmission acting, as one investigator describes, as a nerve transmission “brake”.
At the risk of oversimplification, the NT disturbances described above most likely reflect the complex interactions and functional redundancies characteristic of many essential biological functions, including neurotransmission. Current gene research has identified several abnormalities that may result in abnormal NT structure or function. These early findings support the possibility that OCD may develop by way of several different abnormal processes. Although many investigators believe that the glutamate excess found in OCD patients is the principal result of these events there are, almost certainly, other factors in play (31). Relevant to OCD patients, an understanding of the different forms of NT dysfunction that likely play roles in OCD enables a more focused approach to developing new drugs and therapies to prevent or ameliorate those specific NT disturbances responsible for OCD symptoms. Considering OCD as a group of similar disorders with somewhat different manifestations also may explain why there is so much variability of drug treatment effectiveness, and why trial and error and combination therapy is often needed.
First line drug treatment of OCD
Selected drugs that are commonly used, or show promise, in OCD management are included in this section, and the information will be updated as progress demands.
Most people with OCD are initially managed as outpatients, although hospitalisation may become necessary if a patient becomes dysfunctional with a severe relapse, is causing significant disruption at home or at work, and certainly if there appears to be a risk of suicide. Despite a great deal of research, the results of a great many studies show mixed or even conflicting results for the drugs used in OCD. While this can cause great frustration for patients and their health professionals, an effective treatment strategy is eventually found for most.
The reader must be aware that the information that follows for all types of treatments is intended to provide an overall understanding of potentially useful treatment approaches for people with OCD. Beyond this, there are numerous other aspects of every patient’s case that will be considered by your OCD specialist in order to make treatment recommendations.
The majority of published guidelines for treatment of OCD recommend using a selective serotonin reuptake inhibitor (SSRI), cognitive behavioural therapy (CBT), or a combination of the two, as initial treatment (32). CBT is described later. SSRIs are best known for the treatment of depression and there are a number of SSRIs currently available. In general, the actions of these drugs result in increased availability of serotonin. As already stated, increased serotonin levels lead to reduced glutamate and increased GABA in many parts of the brain. This is thought to be the action responsible for its effectiveness in OCD.
The results of treatment with different SSRIs are essentially comparable and, hence, there is no current consensus about which SSRI is most effective for OCD treatment (33-35). There are, however, differences in their side effect profiles that may be of some importance in individual patients (33, 36, 37). Although clomipramine has usually shown equivalent to somewhat better treatment results compared to SSRIs, its side effect profile makes it a generally less preferred choice as first line therapy (38). Overall, about 40% to 60% of patients treated with SSRIs have satisfactory improvement of their symptoms (39). Investigations of effectiveness using SSRI and CBT combination therapy have also shown greater benefit compared to SSRI, alone (25).
There is existing evidence that those who are unresponsive to a particular SSRI may have benefit from substituting a different one (40). There also is a solid consensus that for greatest effect, patients with OCD generally require SSRI doses in the upper to near maximal range, if tolerated (41) This observation is not restricted to any one SSRI drug and, unfortunately, many OCD patients receiving SSRI turn out to be undertreated. A treatment period of at least 8 to 12 weeks is recommended before concluding that there is lack of efficacy. Numerous patients will prematurely consider their SSRI treatment ineffective and discontinue treatment too soon. To be sure that a trial of an SSRI is adequate, recommended dose ranges can be seen in Table 1.
|Serotonin reuptake inhibitor||Starting dose (mg / day)a||Usual
Table 1. Doses are presented as number of milligrams per day. aSome patients may need to start at half of this dose or less to minimize undesired side effects such as nausea or to accommodate anxiety about taking medications. dSertraline, alone among the SSRIs, is better absorbed with food.
*From Seibel P & Hollander E (2014). F1000 Prime Rep, 6, 68. (41)
As already stated, clomipramine has demonstrated effectiveness as first line therapy for OCD (39). This medication is in a different drug class (tricyclic antidepressant) but also causes serotonin levels to increase. It has been tested head-to-head with different SSRIs with little to no consistent differences in results. As an example, a study that compared SSRI (fluvoxamine) to clomipramine showed mean reductions of Y-BOCS scores after treatment to be 31% and 33% for fluvoxamine and clomipramine, respectively. Clomipramine has also been used with good effect as augmentation strategy with other drugs (42).
Many of clomipramine’s side effects are similar to those of the SSRIs. However, they tend to be more severe and cause more treatment dropouts than the SSRIs. In one study, adverse effects occurred in 62% of SSRI treated individuals and 92% of those taking clomipramine. The most frequent side effects rated by patients as obstacles to treatment were sexual dysfunction (males more than females), weight gain, and sleep disturbances. A closer look at side effects shows a 55% incidence of sexual dysfunction in patients treated with SSRI, compared to 92% of the clomipramine patients. Regarding weight gain, 35% of patients receiving clomipramine gained more than 7 percent of their starting weights. In comparison, this 7% weight increase was seen in only 5% and 9% of patients taking sertraline or fluoxetine, respectively. Serious heart rhythm disturbances and seizures, while uncommon with clomipramine, are much less likely with SSRIs. Given the frequency and degrees of side effects with clomipramine, an SSRI is usually preferred for the initial medication trial, particularly if long-term therapy is anticipated (32, 43, 44).
 The Y-BOCS is a scale that rates severity of OCD and is the most widely used assessment tool for OCD. It can be used to measure change of OCD severity such as before and after a treatment, and also to compare treatments. Its OCD scores are: 0-7 subclinical; 8-15 mild; 16-23 moderate; 24-31 severe, and 32-40 extreme.
 Response inhibition refers to the suppression of actions that are inappropriate in a given context and that interfere with goal-driven behavior.
 Augmentation refers to the addition of a drug to existing drug treatment if the combination has better effectiveness. This must be done with some caution when clomipramine is added to most SSRIs because of potentially dangerous effects on drug levels and side effects.
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